Psychobiology and Psychopharmacology Flashcards
Mood Disorders/Depressed Symptoms
- Depression may be due to decreased levels of 5HT and/or NE. Most involved circuit is the locus coeruleus.
- Bipolar may be due to interactions between NE, DA, 5HT, ACh, GABA, and peptides
Anxiety Disorders/Anxious Symptoms
- Elevated 5HT and NE, and decreased GABA
2. Raphe Nucleus is most involved circuit
Cognitive Disorders
- ADHD: Dysregulation of attention, activity, and impulsivity. Circuits involved include dorsal anterior cingulate cortex, dorsal lateral prefrontal cortex, and orbital frontal cortex.
- Dysregulation involves DA, NE, and other NTs
Dementia Disorders
- Multi-factorial contributors including amyloid plaques and tau, metabolic, and oxygenation issues
Dopamine
- Excitatory NT important in controlling thoughts and emotions, in frontal cortex, mesocortical tract, and are involved in attention, focus, and depression.
- Controls complex movement in the nigrostriatal DA pathway
- Mesolimbic DA to nucleus accumbens involved with pleasurable behaviors; elevated DA here associated with psychosis
- Tuberoinfundibular pathway: prolactin secretion
Norepinephrine
- Located predominantly in the locus coeruleus
- In frontal cortex regulates mood, attention, concentration (alpha-2 receptors)
- In limbic cortex influences emotions and energy; into cerebellum mediates tremors
- In Brainstem affects blood pressure and innervates heart
- Excitatory NT that helps elevate mood, modulate attention and fatigue
- May also contribute to anxiety disorders
5HT receptors
- Located mostly in the raphe nucleus with projections to:
- Frontal Lobe: Affects mood and depression
- Basal Ganglia: Especially 5HT2A, control of movements and obsessions/compulsions
- Limbic Area: Especially 5HT2A and 5HT2C, related to anxiety and panic
- Hypothalamus: 5HT3 receptors related to appetite and sleep (Mirtazipine)
- Spinal Cord: Influence sexual response and gut
- Peripheral: 5HT3 and 5HT4 receptors in the gut regulate appetite as well as GI motility (after a while, receptors down regulate and, nausea goes away)
GABA
Inhibitory NT
Works to sedate and calm
ACh
Plays a role in memory and cognition
Held in balance with dopamine in the substantia nigra
Gutamate
Primary Excitatory NT
CYP 450 1A2
- Inhibited by SSRI fluvoxamine; therefore increases the levels of theophylline.
- Cigarette smoking induces 1A2, increasing the elimination olanzapine; if pt decreases or quits smoking, dose adjustment needed (EXAM LOVES THIS QUESTION).
CYP 2C19
Reduced activity in 20% of Asian persons, ~5% in Caucasians
CYP 2D6
- Inhibited by fluoxetine, paroxetine, and bupropion.
- If switching from TCA to SSRI, it will have elevated blood levels of TCA who depend on 2D6 for metabolism
- Induction of metabolism of hydrocodone, morphine, and tramadol so will affect pain control.
CYP 3A4 Inhibition
- Inhibited by some SSRIs, nefazodone, and grapefruit juice
- Some BZO levels will rise, such as alprazolam when given with fluoxetine
- Inhibited by erythromycin, will therefore affect carbamazepine level. Use zithromax instead
CYP 3A4 Induction
- Carbamazepine, effecting oral contraceptive levels, as well as the level of carbamazepine itself.
- 3A4 induction greatly affects methadone
- Induced by St. John’s Wort
Exogenous estrogen and Lamictal
-Exogenous estrogen in the form of oral contraception induces 1A4, cutting lamotrigine levels by 50%.
Lithium and NSAIDs
Lithium levels increase with inhibition of prostaglandins, so Ibuprofen will effect levels, but ASA, Sulindac, and Tylenol will not.
CATIE
Clinical Antipsychotic Trials in Intervention Effectiveness
- Patients were walking
- Atypicals are still good, but they weren’t the dream med that we thought they would be.
STEP-BD
Treatment Enhancement Program for Bipolar Disorder
Star-D
Sequenced Treatment Alternatives to Relieve Depression
-Still have a lot of residual depression that wasn’t getting treated.
Typical Antipsychotics MOE
D2 blockade in the mesolimbic and mesocortical tract
Typical Antipsychotics SEs
Sedation/wt gain: Histamine blockade
Orthostatic hypotension/drowsiness: Alpha 1 blockade
Increased Prolactin: D2 blockade in the tuberoinfundibular tract
Anti-Cholinergic effects: Muscarinic blockade
EPS: D2 blockade in nigrostriatal tract
Treatments for EPS
Change med
Lower dose
Benztropine (Cogentin)
Typical Antipsychotics Long-term SEs
Permanent effects on movement seen
TD not reversible
Neuroleptic Malignant Syndrome
Neuroleptic Malignant Syndrome
Life threatening complication of antipsychotics
Usually develops within the first 2 weeks of use (90%)
Also seen in Parkinson’s with abrupt levodopa withdrawal
S & S: (HOT, STIFF and OUT OF IT)
-Autonomic instability with hyperthermia
-Muscle rigidity/dystonia
-Extreme mental status change/confusion
Atypical Antipsychotics MOA
D2 and 5HT blockade in brain
- Decreased risk of EPS
- Decreased emergence rates of long-term side effects, including tardive dyskinesias
Dosing Clozapine
May cause agranulocytosis
Rigorous dosing and monitoring
12.5 mg for first dose; thereafter, divided dose
Increase by 25-50 mg per day as tolerated, to 300 to 400 mg per day; maximum is 900 mg per day
Monitoring with Clozapine
Weekly CBC x 6 months
Biweekly x 6 months
monthly after that for rest of life
Clozapine Testing Thresholds
If WBC 2.0 or Neuts
Unique to Risperdal
May cause szr
Contraindicated in preggers
Increased prolactin
Sexual SEs
Risperidone Depot
Every 2 weeks; must be reconsituted and refrigeration
No loading dose option; 3 weeks to max effect
Paliperidone (Invega) Depot
No need for po formulations
Loading dose options
Small needle and volume
q4week inj; costs, injection site reaction
Olanzapine Depot
- Loading dose options
- Cost and needle size are problems
- Post injection delirium (pt should wait around for 3 hours post-injection
Abilify Depot
Q4Weeks
Costs problematic
gluteal only
Metabolic Goals with Antipsychotics
LDLs 60 for men, > 50 for women
BP goal is 120/80
Diagnostics for Metabolic Syndrome
Any 3: Abdominal girth: > 37 in males and >31.5 for women or TG > 150 or HDL 130/85 or on current HTN med or FBG > 100, or prior type II DM diagnosis
HEAT MADE HI
Symptoms of NMS: Hyperthermia Elevated CK Altered Mental Status Tachycardia Mutism Akinesia Diaphoresis Elevated myoglobin Hypertension Irregular pulse
Treatment for NMS
Fatal if left untreated: D/C neuroleptics Hydrate O2 Cooling blanket DANTROLENE (EXAM WANTS THIS ANSWER)
Hot, Stiff, and out of it
Classic Triad for NMS:
Mental status change/confusion
Muscle rigidity/dystonia
Autonomic Instability
Tricyclic eliminated by:
2D6
SRI: Selective Reuptake Inhibitors
Nefazodone
Trazodone
Bupropion
Viibryd and Brintellix
5HT1A partial agonist
- They turn the dopamine brake off
- -Allows patient to feel pleasure
- Gets rid of need for Abilify and BuSpar to enhance your antidepressant
SNRIs
Venlafaxine: Inc in BP at higher doses
Duloxetine
Desvenlafaxine
SRIs and SSRI class side effects and clinical pearls
Never give at night
Sexual dysfunction
Initial nausea subsided with receptor downregulation
Prozac clinical pearls
Long half-life
Stimulating
Younger people mania?
Sexual side effects
Paxil (Paroxetine)
Great for anxiety
Only SSRI in Cat D, no use in preggers
Horrible withdrawal syndrome
Citalopram (Celexa)
Cardiac effects necessitate decreased doses
Prolonged QTc leading to Torsades de pointes and sudden death
Sertraline (Zoloft)
Great for elderly
Easily titrated
Escitalopram (Lexapro)
More effective than Citalopram, fewer side effects
Best medication for bipolar maintenance
Lithium
Exam wants to know firsts
Clozaril first SGA
Lithium first treatment for bipolar
Prozac first SSRI
Therapeutic blood level for acute treatment
1.2 mEq/L
When to check Li level
12 hours after the last dose after 5 days of stable dosing
Cautions with Li
ASA or APAP for over the counter analgesic Ibuprofen can increase serum levels Ca channel blockers are contraindicated Use diuretics with caution Maintain steady hydration levels
LFTs with Depakote
Before first dose
3 and 6 months out
BuSpar shortcomings
Dosed tid or bid, and takes a long time to get going
Drugs for Parkinson’s
1st line: Levodopa is gold standard 2nd line: Acetylcholine antagonists 3rd line: Dopamine agonists -pramipexole -ropinirole -pergolide
Acetylcholine antagonists for Parkinson’s
Benztropine (Cogentin)
Trihexyphenidyl (Artane)
Amantadine (Symmetrel)
Selegline (Eldepryl)
Drugs to reduce levodopa-induced dyskinesias
COMT enzyme inhibitors:
- Tolcapone (Tasmar)
- Entacapone (Comtan)
Sleep Regulator
Ventrolateral preoptic nucleus in the hypothalamus inhibits brainstem arousal
When does REM start?
REM starts 80-100 minutes after sleep initiation
Sleep hygiene points
No screens
Dark and cool
Routine
No caffeine
